Abstract

The effects of γ-hexachlorocyclohexane (γ-HCH) and its α, β and δ isomers on the γ-aminobutyric acid (GABA) responses of human α1β3γ2S and α6β3γ2S GABA_A receptors expressed in Xenopus oocytes were examined by conventional two-electrode voltage-clamp techniques. γ-HCH induced partial inhibition of EC₅₀ GABA responses, whereas the α and δ isomers produced potentiation of EC₂₀GABA currents. In contrast, β-HCH had no effect on GABA currents, even at concentrations as high as 100 μM. The effects of the active HCH isomers were not influenced by alpha subunit composition because there was no significant difference in either the inhibition or potentiation of α1β3γ2S or α6β3γ2S GABA_A receptors. δ- and γ-HCH antagonized picrotoxin inhibition and caused displacement of specific [³⁵S]t-butylbicyclophosphorothionate binding. δ-HCH potentiation was found to be additive with steroid, loreclezole and lanthanum potentiation, but nonadditive with potentiation by pentobarbital and propofol, which suggested that its activity was linked to the barbiturate site.